NPC1_PIG
ID NPC1_PIG Reviewed; 1277 AA.
AC P56941;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=NPC intracellular cholesterol transporter 1 {ECO:0000250|UniProtKB:O15118};
DE AltName: Full=Niemann-Pick C1 protein {ECO:0000303|PubMed:11796528};
DE Flags: Precursor;
GN Name=NPC1 {ECO:0000250|UniProtKB:O15118};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11796528; DOI=10.1210/endo.143.2.8640;
RA Gevry N., Lacroix D., Song J.H., Pescador N., Dobias M., Murphy B.D.;
RT "Porcine Niemann Pick-C1 protein is expressed in steroidogenic tissues and
RT modulated by cAMP.";
RL Endocrinology 143:708-716(2002).
CC -!- FUNCTION: Intracellular cholesterol transporter which acts in concert
CC with NPC2 and plays an important role in the egress of cholesterol from
CC the endosomal/lysosomal compartment. Unesterified cholesterol that has
CC been released from LDLs in the lumen of the late endosomes/lysosomes is
CC transferred by NPC2 to the cholesterol-binding pocket in the N-terminal
CC domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group
CC buried in the binding pocket. Binds oxysterol with higher affinity than
CC cholesterol (By similarity). May play a role in vesicular trafficking
CC in glia, a process that may be crucial for maintaining the structural
CC and functional integrity of nerve terminals (Probable).
CC {ECO:0000250|UniProtKB:O15118, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000250|UniProtKB:O15118};
CC -!- SUBUNIT: Interacts (via the second lumenal domain) with NPC2. Interacts
CC with TMEM97. Interacts with TIM1. {ECO:0000250|UniProtKB:O15118}.
CC -!- SUBCELLULAR LOCATION: Late endosome membrane
CC {ECO:0000305|PubMed:11796528}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O15118}. Lysosome membrane
CC {ECO:0000305|PubMed:11796528}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O15118}.
CC -!- TISSUE SPECIFICITY: Detected in corpus luteum, granulosa cells and
CC adrenal gland. {ECO:0000269|PubMed:11796528}.
CC -!- DOMAIN: A cysteine-rich N-terminal domain and a C-terminal domain
CC containing a di-leucine motif necessary for lysosomal targeting are
CC critical for mobilization of cholesterol from lysosomes.
CC {ECO:0000250|UniProtKB:O15118}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:O15118}.
CC -!- SIMILARITY: Belongs to the patched family. {ECO:0000305}.
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DR EMBL; AF169635; AAD47090.1; -; mRNA.
DR RefSeq; NP_999487.1; NM_214322.1.
DR AlphaFoldDB; P56941; -.
DR SMR; P56941; -.
DR STRING; 9823.ENSSSCP00000004014; -.
DR PaxDb; P56941; -.
DR PeptideAtlas; P56941; -.
DR PRIDE; P56941; -.
DR GeneID; 397591; -.
DR KEGG; ssc:397591; -.
DR CTD; 4864; -.
DR eggNOG; KOG1933; Eukaryota.
DR InParanoid; P56941; -.
DR OrthoDB; 731120at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:1905103; C:integral component of lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005635; C:nuclear envelope; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0015485; F:cholesterol binding; ISS:UniProtKB.
DR GO; GO:0005319; F:lipid transporter activity; IEA:InterPro.
DR GO; GO:0032934; F:sterol binding; IBA:GO_Central.
DR GO; GO:0008206; P:bile acid metabolic process; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0030301; P:cholesterol transport; ISS:UniProtKB.
DR GO; GO:0030299; P:intestinal cholesterol absorption; IBA:GO_Central.
DR GO; GO:0032367; P:intracellular cholesterol transport; ISS:UniProtKB.
DR GO; GO:0007041; P:lysosomal transport; ISS:UniProtKB.
DR GO; GO:0006486; P:protein glycosylation; ISS:UniProtKB.
DR GO; GO:0015918; P:sterol transport; IBA:GO_Central.
DR InterPro; IPR004765; NPC1-like.
DR InterPro; IPR032190; NPC1_N.
DR InterPro; IPR003392; Ptc/Disp.
DR InterPro; IPR000731; SSD.
DR Pfam; PF16414; NPC1_N; 1.
DR Pfam; PF02460; Patched; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR TIGRFAMs; TIGR00917; 2A060601; 1.
DR PROSITE; PS50156; SSD; 1.
PE 2: Evidence at transcript level;
KW Cholesterol metabolism; Disulfide bond; Endosome; Glycoprotein;
KW Lipid metabolism; Lipid transport; Lysosome; Membrane; Reference proteome;
KW Signal; Steroid metabolism; Sterol metabolism; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1277
FT /note="NPC intracellular cholesterol transporter 1"
FT /id="PRO_0000023263"
FT TOPO_DOM 23..269
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 291..350
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 351..371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 372..621
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 622..642
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 643..653
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 654..674
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 675..677
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 678..698
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 699..734
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 735..755
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 756..759
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 760..780
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 781..832
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 833..853
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 854..1097
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1098..1118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1119..1123
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1124..1144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1145
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1146..1166
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1167..1194
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1195..1215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1216..1226
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 1227..1247
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1248..1277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 620..785
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 175..205
FT /note="Important for cholesterol binding and cholesterol
FT transfer from NPC1 to liposomes"
FT /evidence="ECO:0000250"
FT REGION 1274..1277
FT /note="Required for location in lysosomes"
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT MOTIF 1274..1277
FT /note="Di-leucine motif"
FT BINDING 41
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT BINDING 79
FT /ligand="cholesterol"
FT /ligand_id="ChEBI:CHEBI:16113"
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT SITE 108
FT /note="Important for cholesterol binding"
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT CARBOHYD 70
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 122
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 415
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 452
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 478
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 898
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 916
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 931
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 961
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 968
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1028
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1063
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 25..74
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 31..42
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 63..109
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 75..113
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 97..238
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 100..160
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 177..184
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 227..243
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 240..247
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 468..479
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 516..533
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 909..914
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 956..1011
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 957..979
FT /evidence="ECO:0000250|UniProtKB:O15118"
FT DISULFID 967..976
FT /evidence="ECO:0000250|UniProtKB:O15118"
SQ SEQUENCE 1277 AA; 141963 MW; 2C80D300889F02EB CRC64;
MSARGPAFGL LLLLLCPVQV FSQSCVWYGE CGIASGDKRY NCRYSGPPKP LPEDGYDLVQ
ELCPGFFFGN VSLCCDVQQL RTLKDNLQLP LQFLSRCPSC FYNLMNLFCE LTCSPRQSQF
LNVTATEDYV DPVTNQTKTN VKELEYYVGE TFANAMYNAC RDVEAPSSNE KALGLLCGRE
AQACNATNWI EYMFNKDNGQ APFTITPIFS DLPTHGMEPM NNATKGCDES VDEVTGPCSC
QDCSIVCGPK PQPPPPPVPW RILGLDAMYV IMWSSYMAFL IVFFGAFFAV WCYRKRYFVS
EYTPIDGNIA FSVNSSDKGQ AFCCDPLGAA FERGLRRLFA QWGAFCVRHP GCVVFFSLAF
IVACSSGLVF IRVTTDPVDL WSAPGSQARR EKEYFDTHFG PFFRMEQLII RATNNQSHIY
HPYPAGADVP FGPPLSRDIL HQVLDLQTAI ENITASYNNE TVTLQDICLA PLSPYNKNCT
ILSVLNYFQN SHSVLDHQVG DFFFVYADYH THFLYCVRAP ASLNDASLLH DPCLGTFGGP
VFPWLVLGGY DDQNYNNATA LVITFPVNNY YNDTEKLQRA QAWESEFINF VKNYKNPNLT
ISFMAERSIE DELNRESNSD LFTILISYAI MFLYISIALG HIKSCSRLLV DSKISLGIAG
ILIVLSSVAC SLGIFSYIGV PLTLIVIEVI PFLVLAVGVD NIFILVQTYQ RDERLQGETL
DQQLGRVLGE VAPSMFLSSF SETVAFFLGG LSVVPAVHTF SLFAGMAVLI DFLLQITCFV
SLLGLDIKRQ EKNRLDVVCC VQGAEDGAGV QASESCLFRF FKNSYAPLLL KDWMRPIVIA
VFVGVLSFSI AVLNKVEIGL DQSLSMPDDS YVMDYFQSLS RYLHAGPPVY FVVEEGHNYT
SLKGQNMVCG GLGCNNDSLV QQIFTAAQLD NYTRIGFAPS SWIDDYFDWI KPQSSCCRVY
NSTDQFCNAS VVDPTCIRCR PLTSEGKQRP QGEDFMRFLP MFLSDNPNPK CGKGGHAAYS
SAVNILGNGS GVGATYFMTY HTVLQASADF IDAMQKARLI ASNITRTMGL EASSYRVFPY
SVFYVFYEQY LTVIDDTIFN LGVSLGAIFL VTVVLMGCEL WATVIMCVTI AMILVNMFGV
MWLWGISLNA VSLVNLVMSC GISVEFCSHI TRAFTLSTKG SRVDRAEEAL AHMGSSVFSG
ITLTKFGGIV VLAFAKSQIF QIFYFRMYLA IVLLGATHGL IFLPVLLSYI GPSINKAKSL
ATQERYKGTE REQLLNF
